Fas-Fas ligand interactions are essential for the binding to and killing of activated macrophages by γδ T cells
Fas-Fas ligand interactions are essential for the binding to and killing of activated macrophages by γδ T cells
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DOI：
10.4049/jimmunol.173.6.3660
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发表时间：
2004-09-15
影响因子：
4.4
通讯作者：
Carding, SR
中科院分区：
文献类型：
--
作者：
Dalton, JE;Howell, G;Carding, SR
γ δ T细胞在通过消除活化的巨噬细胞群体来解决宿主对感染的免疫应答中具有直接作用。巨噬细胞反应性存在于γ δ T细胞的V γ 1/V66.3亚群内，其具有在感染单核细胞增生李斯特菌（Lm）后杀死活化的巨噬细胞的能力。然而，目前尚不清楚γ δ T细胞巨噬细胞杀伤活性是如何调节的，或者γ δ T细胞使用什么效应机制来杀死活化的巨噬细胞。使用巨噬细胞-T细胞共培养系统，其中来自初始或Lm感染的TCR δ（-/-）小鼠的腹腔巨噬细胞与来自野生型和Fas配体（FasL）缺陷小鼠（gld）的脾细胞孵育，显示V γ 1 T细胞结合巨噬细胞的能力依赖于Fas-FasL相互作用。抗TCR和FasL Ab的组合完全消除了V γ 1 T细胞对活化的巨噬细胞的结合和杀伤。此外，共聚焦显微镜显示Fas和TCR共定位于与巨噬细胞接触的V γ 1 T细胞上。总的来说，这些研究确定了Fas-FasL的辅助或辅助受体样功能，其对于V γ 1 T细胞与活化的巨噬细胞的相互作用以及在病原体诱导的免疫应答的消退阶段期间消除它们是必不可少的。
gammadelta T cells have a direct role in resolving the host immune response to infection by eliminating populations of activated macrophages. Macrophage reactivity resides within the Vgamma1/V66.3 subset of gammadelta T cells, which have the ability to kill activated macrophages following infection with Listeria monocytogenes (Lm). However, it is not known how gammadelta T cell macrophage cytocidal activity is regulated, or what effector mechanisms gammadelta T cells use to kill activated macrophages. Using a macrophage-T cell coculture system in which peritoneal macrophages from naive or Lm-infected TCRdelta(-/-) mice were incubated with splenocytes from wild-type and Fas ligand (FasL)-deficient mice (gld), the ability of Vgamma1 T cells to bind macrophages was shown to be dependent upon Fas-FasL interactions. Combinations of anti-TCR and FasL Abs completely abolished binding to and killing of activated macrophages by Vgamma1 T cells. In addition, confocal microscopy showed that Fas and the TCR colocalized on Vgamma1 T cells at points of contact with macrophages. Collectively, these studies identify an accessory or coreceptor-like function for Fas-FasL that is essential for the interaction of Vgamma1 T cells with activated macrophages and their elimination during the resolution stage of pathogen-induced immune responses.